Substituted quinolines and leucotriene antagonism treatment therewith

Abstract

PCT No. PCT/DK90/00201 Sec. 371 Date Jan. 29, 1992 Sec. 102(e) Date Jan. 29, 1992 PCT Filed Aug. 9, 1990 PCT Pub. No. WO91/03466 PCT Pub. Date Mar. 21, 1991. <IMAGE> (I) The present invention relates to hitherto unknown compounds of formula, in which m and n stand for an integer from 0-5, p stands for 0 or 1, and q stands for an integer from 0-4, R1 and R2 are the same or different and stand for hydrogen, halogen, nitro, amino, alkyl or alkoxy; R3 is hydroxy, hydrogen, straight or branched, saturated or unsaturated C1-C6 alkyl; R5 stands for an acidic group, e.g. carboxy, 1-H tetrazolyl, a sulphonic acid group, a sulfamyl group, a sulphinic acid group, or a hydroxamic acid group; R4 and R6 are the same or different and stand for hydrogen, straight or branched, saturated or unsaturated, unsubstituted or substituted C1-C6 alkyl groups or unsubstituted or substituted aralkyl groups. R7 has the same meaning as R5 or represents a hydrogen, straight or branched, saturated or unsaturated, unsubstituted or substituted C1-C6-alkyl group. The present compounds are of value in the human and veterinary practice as lipoxygenase inhibitors and/or leukotriene antagonists.

What we claim is: 
     
       1. A compound of the formula I ##STR16## in which m and n stands for an integer from 0-5, p stands for 0 or 1, and q stands for an integer from 0-4, R 1  and R 2  are the same or different and stand for hydrogen, halogen, nitro, amino, alkyl or alkoxy; R 3  is hydroxy, hydrogen, straight or branched, saturated or unsaturated C 1-6  alkyl; R 5  stands for carboxy, 1H-tetrazolyl, a sulphonic acid group, a sulfamyl group, a sulphinic acid group, or a hydroxamic acid group; R 4  and R 6  are the same or different and stand for hydrogen, straight or branched, saturated or unsaturated C 1-6  alkyl groups or aralkyl groups; R 7  has the same meaning as R 5  or represents a hydrogen, straight or branched, saturated or unsaturated C 1-6  -alkyl group; and pharmaceutically acceptable, non-toxic salts and in-vivo hydrolyzable alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl or aminoacyloxyalkyl esters thereof. 
     
     
       2. A salt according to claim 1, in which the salt is selected from the group consisting of salts formed with hydrochloric, hydrobromic and hydroiodic acid, phosphoric acid, sulphuric acid, nitric acid, p-toluenesulphonic acid, methanesulphonic acid, formic acid, acetic acid, propionic acid, citric acid, tartaric acid, and maleic acid, alkali metal salts and alkaline earth metal salts, as well as salts with ammonia and non-toxic amines. 
     
     
       3. A compound of claim 1 which is selected from the group consisting of the following acids or esters, their salts and pure enantiomeric forms: (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (2R,3R;2S,3S)-3-[4-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (2R,3R;2S,3S)-3-[2-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (2R,3R)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (S,R)-2-[3-(2-quinolylmethyloxy)-anilino]-2-phenyl acetic acid;   (S,R)-2-[4-(2-quinolylmethyloxy)-anilino]-2-phenyl acetic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(2-fluorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(2-chlorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(2-methoxyphenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(3-chlorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-fluorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(4-methylphenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(4-fluorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(4-chlorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(4-methoxyphenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(4-nitrophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(2,5-difluorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(2,4-difluorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(2,4-dichlorophenyl)propionic acid;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-phenyl propionic acid ethyl ester;   (2R,3R;2S,3S)-3-[3-(2-quinolylmethyloxy)-anilino]-2-hydroxy-3-(4-methoxyphenyl)propionic acid ethyl ester;   
     
     
       4. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier therefor. 
     
     
       5. A method of inhibiting 5-lipoxygenase and thereby the production and effects of leukotrienes in a host in need of such inhibition, said method comprising administering to said host an effective amount of a compound according to claim 1.